title: Twist1-induced invadopodia formation promotes tumor metastasis.
abstract: The Twist1 transcription factor is known to promote tumor metastasis and induce Epithelial-Mesenchymal Transition (EMT). Here, we report that Twist1 is capable of promoting the formation of invadopodia, specialized membrane protrusions for extracellular matrix degradation. Twist1 induces PDGFRα expression, which in turn activates Src, to promote invadopodia formation. We show that Twist1 and PDGFRα are central mediators of invadopodia formation in response to various EMT-inducing signals. Induction of PDGFRα and invadopodia is essential for Twist1 to promote tumor metastasis. Consistent with PDGFRα being a direct transcriptional target of Twist1, coexpression of Twist1 and PDGFRα predicts poor survival in breast tumor patients. Therefore, invadopodia-mediated matrix degradation is a key function of Twist1 in promoting tumor metastasis.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Eckert
authors.forename: Thinzar M
authors.initials: TM
authors.lastname: Lwin
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chang
authors.forename: Jihoon
authors.initials: J
authors.lastname: Kim
authors.forename: Etienne
authors.initials: E
authors.lastname: Danis
authors.forename: Lucila
authors.initials: L
authors.lastname: Ohno-Machado
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D022081:Cell Surface Extensions / Q000378:metabolism / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018909:src Homology Domains / Q000235:genetics
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D009687:Nuclear Proteins; C478582:SH3PXD2A protein, human; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D020796:Receptor, Platelet-Derived Growth Factor alpha